Description: (Applicant's Description) The Transgenic/Knockout Shared Core Resource is an expansion from the existing transgenic mouse core laboratory to include targeted gene disruption using homologous recombination in embryonic stem (ES) cells and the generation of "knockout" mice. The facility will also support the in vitro differentiation of ES cells. This core, which began operation in 1990, now consists of has an ES cell/targeted gene disruption facility and a microinjection laboratory. The core provides all the necessary services to support the generation, maintenance, breeding and preservation of transgenic and germ line positive knockout mice. Over the past four and one-half years, the transgenic component of this resource has served 25 different Cancer Center Investigators and generated 241 transgenic founders representing 44 constructs. The new ES cell/gene disruption facility has recently generated four germ line positive knockout mouse lines. In addition, the ES cell laboratory provides technical expertise in growth of ES cells and targeted gene disruption using homologous recombination and instruction of investigators in methods of in vitro ES cell differentiation. The core also provides embryo cryopreservation, strain rederivation, training of Cancer Center investigators, their graduate and postdoctoral students in transgenic technology, models and genetics. This component also provides colony management and maintenance, automated pedigree management, and breeding of all transgenic founders, knockout and experimental breeding colonies. The Transgenic/Knockout core presents a comprehensive service available to Cancer Center investigators for manipulation of the mouse genome. The primary goal is to maintain a state-of-the-art Transgenic/Knockout facility in the Cancer Center that is affordable and accessible to investigators for their studies in cancer biology.